HIV is the etiological agent of AIDS and predisposes to acquired oral infections such as HIV gingivitis, periodontitis, candidiasis and viral infections. In particular, periodontal diseases represent a significant bacterial challenge to the oral tissues and are likely to alter the function of resident immunocompetent cells during retroviral infection. This proposal is aimed to studying the pathogenesis of oral lesions immediately following infection and during the latent period and is based on virus infection and/or alteration of macrophages in the gingival mucosa. These studies cannot be completed in humans since, in humans, the time of exposure and the viral inoculum cannot be simultaneously determined. Protocols will be investigated in the Simian Immunodeficiency Virus (SIV)/macaque model which closely resembles HIV infection in humans. This model system is established in our laboratory. To the end the following specific aims are planned: 1. Immunological and molecular probes of SIV and antigen presenting cells (APC) will be used to determine the presence of productive infection and cellular compartmentalization of viral infection is isolated gingival macrophages and tissue samples collected from SIV infected macaques. 2. Macrophage to T cell and B cell ratios in the gingiva of SIV infected animals with pre-existing or induced periodontal diseases will be determined to assess the distribution of immunocompetent cells in these tissues as compared to uninfected animals. 3. Gingival macrophages from animals in each experimental group will be studied through light and immuno-electron microscopic evaluation of cell surface membrane receptors and differentiation antigens known to be associated with macrophage function and maturation. These cellular characteristics will be compared to ultrastructural morphological indicators of macrophage activation and further related to the presence of pre-existing or induced periodontal diseases. These studies should assist in determining the direction for future research by aiding the selection of appropriate assays to measure immune function related to retroviral associated oral diseases. These studies should also result in a greater understanding of the pathogenesis of lentiviral infections in primates. Appropriate correlates to HIV related oral diseases in humans might result, eventually leading to improved strategies of therapeutic intervention.